Our work regarding the use of gold nanorods as contrast agents for photoacoustic tracking of stem cells has been just published (or here*). You can find all the technical details of the work there, so I will try to explain here the work for the readers who are not very familiar with our field.

It is important to have the appropriate tools to evaluate safety and efficacy of regenerative medicine therapies in preclinical models before they can be translated to the clinics. This is why there is an interest in developing new imaging technologies that enable real time cell tracking with improved sensitivity and/or resolution. This work is our contribution to this field.

To distinguish therapeutic cells from the patient’s own cells (or here from the mouse’s own cell), the therapeutic cells have to be labelled before they are implanted. It is well known, that biological tissue is more transparent to some regions of the light spectrum than others. This fact is very easy to try at home (or at your favourite club): if you put your hand under a green light, no light will go through it, whilst doing the same under a red light the result will be very different. That means that red light is less absorbed by our body. Near infrared light is even less absorbed and this is why this region of the spectrum is ideal for in vivo imaging. Therefore, we made our cells to absorb strongly in the near infrared so we can easily distinguish them.

Gold nanoparticles of different sizes and shapes (synthesis and picture by Joan Comenge).

To do this, we labelled cells with gold nanoparticles. Interestingly, the way gold nanoparticles interact with light depends on how their electrons oscillate. That means that size and shape of the nanoparticles determine their optical properties, and this is one of the reasons why we love to make different shapes of nanoparticles. In particular, gold nanorods strongly absorb in the near infrared and they are ideal contrast agents for in vivo imaging.

Figure reproduced from: The production of sound by radiant energy; Science 28 May 1881; DOI: 10.1126/science.os-2.49.242

We have now cells that interact with light in a different way than the tissue. The problem is that light is scattered by tissue, so resolution is rapidly lost as soon as you try to image depths beyond 1 mm. Obviously, this is not the best for in vivo imaging. Luckily for us, Alexander Graham Bell realised 130 years ago that matter emits sounds when is irradiated by a pulsed light. This is known as the photoacoustic effect and it has been exploited recently for bioimaging. Photoacoustic imaging combines the advantages of optical imaging (sensitivity, real-time acquisition, molecular imaging) and the good resolution of ultrasound imaging because ultrasounds (or phonons), contrarily to photons, are not scattered by biological tissue.

Silica-coated gold nanorods inside cells

To optimise the performance of our gold nanorods, we coated them with silica. Silica is glass and therefore it protects the gold core without interfering with its optical properties. This protection is required to maintain gold nanorods isolated inside cells since nanorods are entrapped in intracellular vesicles, where they are very packed. The absence of a protective coating ultimately would result in a broader and less intense absorbance band, which would be translated to a less intense photoacoustic signal and consequently a lower sensitivity in cell detection. This of special importance in our system, a photoacoustic imaging system developed by iThera Medical which uses a multiwavelength excitation to later deconvolute the spectral information of the image to find your components of interest. Thus, narrow absorption bands helps to improve the detection sensitivity even further. With this we demonstrated that we were able to monitor a few thousand nanorods labelled-cells with a very good 3D spatial resolution for 15 days. This allowed for example to see how a cell cluster changed with time, see how it grows or which regions of the cell cluster shows the highest cell density. In addition, this work opens the door to new opportunities such as multilabelling using gold nanorods of different sizes and consequently different optical properties to observe simultaneously different type of cells. We also believe that not only stem cell therapies, but also other fields that are interested in monitoring cells such as cancer biology or immunology can benefit from the advances described in our work.

You can find the original publication here (or here*).
All the datasets are available via Figshare.

The UKRMP Safety Hub was established alongside a further four Hubs to address the number of developmental challenges which need to be overcome to successfully translate promising discoveries in the field of regenerative medicine for the benefit of patients. To ensure research connects seamlessly from discovery science through to clinical and commercial application, BBSRC, EPSRC and MRC together formed the UKRMP across UK universities and research institutions. Cell tracking with nanoparticles is a major component of the Safety Hub.

The meeting will include significant time for discussions regarding the achievements, potential, and limitations of nanoparticles for cell tracking and the implications with respect to stem cell tracking in animal models and humans.

We are accepting abstracts for both oral and poster presentations; if you would like to submit an abstract please follow the instructions on the guidance document and send to chutch@liv.ac.uk no later than30th June 2015.

Those who are successful will be notified and required to register for the meeting. Registration will open shortly after the Abstract Submission deadline.

Imaging Workshop and Prelaunch of the University of Liverpool’s new Centre for Preclinical Imaging

4th September 2013, Sherrington Lecture Theatre 1 (311 on campus map)

During the next academic session, the University of Liverpool will be opening a Centre for Preclinical Imaging. The Centre, which will be based in the Physiology building within the Institute of Translational Medicine, aspires to provide all of the key imaging modalities currently used for small animal whole-body imaging. Apart from providing state-of-the-art imaging facilities for researchers working with small animals, a key aim of the Centre will be to collaborate with physical scientists, including chemists, physicists, engineers, mathematicians and computer scientists, in order to develop multi-modal imaging strategies, next generation imaging technologies and novel imaging probes.

11:00-11:15 Chris Sanderson (Head of the Department of Physiology, University of Liverpool)

“Introducing the University of Liverpool’s Centre for Preclinical Imaging”

“Applications of fluorescence and bioluminescence in small animal imaging”

16:20-16:50 Raphael Lévy (Institute of Integrative Biology, University of Liverpool)

“Photothermal and photoacoustic imaging for cell and small animal imaging”

16:50-1715 Trish Murray (Institute of Translational Medicine, University of Liverpool)

“An overview of the Centre for Preclinical Imaging: current status; predicted timescales for completion and installation of imaging platforms; information on how it will operate.”

*Biographies of external speakers

Dr Harald Groen Dr. Harald Groen is an application scientist at MILabs, supporting scientists using MILabs’ SPECT, PET and multi-modal imaging devices. He studied BioMedical Engineering and obtained his PhD at the Erasmus MC, Rotterdam, the Netherlands on shear stress and atherosclerosis. After his PhD he was a post-doctoral researcher at the department of Nuclear Medicine, studying neuroendocrine tumors with SPECT and PET in animal models. In addition, he was coordinator of the Applied Molecular Imaging Facility of the Erasmus MC, a platform for scientists who share state-of-the-art imaging technology – like ultrasound, micro-CT, MRI, optical, SPECT and PET imaging – and molecular assays for studying biological systems. As such, he has a broad experience in multi-modal preclinical imaging. h.groen@milabs.com

Professor Pai-Chi Li is IEEE Fellow, IAMBE Fellow and AIUM Fellow. He is also Editor-in-Chief of Journal of Medical and Biological Engineering, Associate Editor of Ultrasound in Medicine and Biology, Associate Editor of IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, and on the Editorial Board of Ultrasonic Imaging and Photoacoustics. He has received numerous awards, including the 2012 Distinguished Research Award from National Science Council, the 2011 National Innovation Award, the 2011 Distinguished Innovation Research Reward from National Taiwan University, the 2009 Distinguished Research Award from National Science Council. He was also recipient of the Distinguished Achievement Award in Electrical Engineering: Systems in 1994 for his outstanding academic achievement at the University of Michigan. paichi@cc.ee.ntu.edu.tw

Dr Michael Gyngell is an employee of Agilent Technologies and has the role of European MRI Applications Lab Manager at Agilent’s facility in Oxford. He has a distinguished career in MRI, contributing to the field both as an engineer & scientist, in industry as well as in academia, for over 30 years. He is author or co-author of more than 50 journal articles and many conference proceedings. He has also served on the board of trustees of the ISMRM (International Society of Magnetic Resonance in Medicine). michael.gyngell@agilent.com

Dr Philippe Choquet is a Senior Lecturer in Biophysics and Nuclear Medicine, and since 2011, has been head of the Preclinical Imaging Lab, department of the Strasbourg University Hospitals. He is the author and coauthor of more than 50 papers in peer-reviewed journals as well as more than 100 oral and poster communications in national and international meetings in the field of low field MRI, MR elastography, NMR/MRI of hyperpolarized gases, tomographic reconstruction, small animal scintigraphy and µCT.pchoquet@unistra.fr

Professor Freek Beekman is head of the section Radiation, Detection & Medical Imaging at Delft University of Technology. He has (co-)authored more than 100 peer reviewed journal papers, several book chapters and over 20 patent applications and was presented with several national & international awards for his scientific contributions to biomedical imaging. His research interest includes development of detectors, image reconstruction for SPECT, PET, X-ray CT & hybrid imaging devices. Freek is an editorial board member of the International Journal of Biomedical Imaging and Physics in Medicine & Biology. He is also the founder and CEO of Molecular Imaging Laboratories (www.milabs.com) that markets systems with an unsurpassed spatial and temporal resolution. Recently, MILabs received the Frost & Sullivan Product Innovation Award for VECTor, the first system that performs SPECT and PET imaging simultaneously at sub-mm resolution level. f.beekman@milabs.com

Dr Francois Lassailly is head of the In Vivo Imaging Facility at the London Research Institute – Cancer Research UK, which he started to develop in 2007. After an initial training in Immunology and Cellular Engineering Francois worked for 7 years in different academic and private Cell Therapy laboratories. He then had the opportunity to develop Patient Derived Xenograft models of human leukaemia and to manage the Tumour Biobank of the Paoli Calmettes Institute (regional cancer centre of Marseille, France). He did his PhD at the London Research Institute (LRI – CRUK), working on multimodal and multiscale optical imaging of haematopoietic stem cell niches in the bone marrow during which he initiated the core in vivo imaging activity by implanting 3 imaging modalities. In 2010 he received his PhD and was directly hired by the institute to lead and develop the In Vivo Imaging Facility which is now offering whole body optical imaging (fluorescence and bioluminescence), intravital microscopy, x-ray microCT and high resolution ultrasound. He is now becoming involved with the development of the in vivo imaging facility for the new Francis Crick Institute, which is to open in 2015. Francois.Lassailly@cancer.org.uk

Andor has just published a technical note from Lara Bogart. That follows from their visit of our lab a couple of weeks ago.

Lara Bogart from Raphael Levy’s research group at the Institute of Integrative Biology in University of Liverpool is interested in understanding how magnetic nanoparticles interact with cells; this is important for a range of biomedical applications including diagnosis of disease, hyperthermia therapy and stem cell tracking applications.

There is a growing interest in techniques that allow the in vivo imaging of cells that have been transplanted into animals and humans, which stems from the need for a better understanding of cellular fate in biological processes. Cancer research and cell based therapies are two fields of research that would greatly benefit from real-time non-invasivein vivo cell imaging, allowing the possibility to follow cell migration, distribution and engraftment following transplantation. This would allow the determination of the fate and metastatic potential of cancer cells in animal models, as well as the tracking of cells employed in regenerative therapies (stem cells) or immunotherapy (immune effector cells).

This symposium will be a forum for discussion on the latest research and challenges concerning imaging technologies that make use of nanoparticles as contrast agents for in vivo cell imaging.

We have a range of outstanding speakers from the UK, Switzerland, Belgium, France, Germany, Canada and the USA. The call for abstract is open for both selected talks and posters.